Biomechanics and thermodynamics of nanoparticle interactions with plasma and endosomal membrane lipids in cellular uptake and endosomal escape.
Biomechanics and thermodynamics of nanoparticle interactions with plasma and endosomal membrane lipids in cellular uptake and endosomal escape.
复制标题
DOI：
10.1021/la5015219
复制
发表时间：
2014-07-01
期刊：
影响因子：
--
通讯作者：
Labhasetwar V
中科院分区：
文献类型：
--
作者：
Peetla C;Jin S;Weimer J;Elegbede A;Labhasetwar V
为了有效地用于治疗剂的细胞质递送，经由内吞途径摄取的纳米颗粒（NP）必须有效地运输穿过细胞膜，并且随后从次级内体逃逸。我们假设，在这些过程中涉及的生物力学和热力学相互作用的纳米粒子与血浆和内体膜脂质。使用模型血浆和内体脂质膜，我们比较了由双链表面活性剂双十二烷基二甲基溴化铵（DMAB）或单链表面活性剂十六烷基三甲基溴化铵（CTAB）修饰的聚（d，l-丙交酯-共-乙交酯）组成的阳离子NP与类似大小的阴离子未修饰NP的相互作用。我们在阿霉素敏感的（MCF-7，具有相对流体膜）和耐药的乳腺癌细胞（MCF-7/ADR，具有刚性膜）中验证了我们的假设。尽管他们的阳离子表面电荷，DMAB和CTAB改性的纳米粒子表现出不同的模式的生物物理相互作用：DMAB改性的纳米粒子诱导弯曲的模型质膜，而CTAB改性的纳米粒子凝聚的膜，从而抵制弯曲。未改性的NP对弯曲没有影响。DMAB修饰的NP也诱导模型内体膜的热力学不稳定性，而CTAB修饰和未修饰的NP没有影响。由于质膜的弯曲和内体膜的不稳定分别是NP细胞摄取和内体逃逸的关键生物物理过程，因此我们测试了这些NP的细胞摄取和药物功效。共聚焦成像显示，在敏感和耐药细胞中，DMAB修饰的NP比CTAB修饰或未修饰的NP表现出更大的细胞摄取和从内体逃逸。此外，紫杉醇负载的DMAB修饰的NP甚至在抗性细胞中比CTAB修饰或未修饰的NP或溶液中的药物诱导更大的细胞毒性，证明了DMAB修饰的NP克服抗性细胞中的转运屏障的潜力。总之，与膜脂质的生物力学相互作用参与细胞摄取和核内体逃逸的纳米颗粒。生物物理相互作用的研究可以帮助我们更好地了解膜脂质在细胞摄取和细胞内运输的纳米粒子的作用。
To be effective for cytoplasmic delivery of therapeutics, nanoparticles (NPs) taken up via endocytic pathways must efficiently transport across the cell membrane and subsequently escape from the secondary endosomes. We hypothesized that the biomechanical and thermodynamic interactions of NPs with plasma and endosomal membrane lipids are involved in these processes. Using model plasma and endosomal lipid membranes, we compared the interactions of cationic NPs composed of poly(d,l-lactide-co-glycolide) modified with the dichain surfactant didodecyldimethylammonium bromide (DMAB) or the single-chain surfactant cetyltrimethylammonium bromide (CTAB) vs anionic unmodified NPs of similar size. We validated our hypothesis in doxorubicin-sensitive (MCF-7, with relatively fluid membranes) and resistant breast cancer cells (MCF-7/ADR, with rigid membranes). Despite their cationic surface charges, DMAB- and CTAB-modified NPs showed different patterns of biophysical interaction: DMAB-modified NPs induced bending of the model plasma membrane, whereas CTAB-modified NPs condensed the membrane, thereby resisted bending. Unmodified NPs showed no effects on bending. DMAB-modified NPs also induced thermodynamic instability of the model endosomal membrane, whereas CTAB-modified and unmodified NPs had no effect. Since bending of the plasma membrane and destabilization of the endosomal membrane are critical biophysical processes in NP cellular uptake and endosomal escape, respectively, we tested these NPs for cellular uptake and drug efficacy. Confocal imaging showed that in both sensitive and resistant cells DMAB-modified NPs exhibited greater cellular uptake and escape from endosomes than CTAB-modified or unmodified NPs. Further, paclitaxel-loaded DMAB-modified NPs induced greater cytotoxicity even in resistant cells than CTAB-modified or unmodified NPs or drug in solution, demonstrating the potential of DMAB-modified NPs to overcome the transport barrier in resistant cells. In conclusion, biomechanical interactions with membrane lipids are involved in cellular uptake and endosomal escape of NPs. Biophysical interaction studies could help us better understand the role of membrane lipids in cellular uptake and intracellular trafficking of NPs.
登录
查看更多内容
影响因子：
4.9
作者：
Peetla C;Rao KS;Labhasetwar V
通讯作者：
Labhasetwar V
DOI：
10.1016/j.bbrc.2014.01.107
发表时间：
2014-02-21
影响因子：
3.1
作者：
Asai, Tomohiro;Tsuzuku, Takuma;Oku, Naoto
通讯作者：
Oku, Naoto
DOI：
10.1007/s00249-008-0352-6
发表时间：
2008-11-01
影响因子：
2
作者：
Dennison, Sarah R.;Kim, Young Soo;Phoenix, David A.
通讯作者：
Phoenix, David A.
影响因子：
3.4
作者：
Frederick, Thomas E.;Chebukati, Janetricks N.;Fanucci, Gail E.
通讯作者：
Fanucci, Gail E.
影响因子：
5.8
作者：
Panyam, J;Sahoo, SK;Labhasetwar, V
通讯作者：
Labhasetwar, V